Bone Disorders

Question 1

Osteoblasts

Answer 1

Bone forming cells, secrete bone matrix

Question 2

Osteocytes

Answer 2

Mature bone cells enclosed by bone matrix

Question 3

Osteoclasts

Answer 3

Resorbs bone, releasing Ca2+

Question 4

Two Agents used to treat osteoporosis

Answer 4

Antiresorptive Drugs
- Decrease Bone Loss

Anabolic Agents
- Increase Bone Formation

Question 5

What treats Rickets and Osteomalacia

Answer 5

Vitamin D Preparations

Question 6

What treats Paget’s Disease

Answer 6

Bisphosphonates and Calcitonin

Question 7

Bisphosphonates
- Examples

Answer 7

Aminobisphosphonates:
- Alendronate, Risedronate, Pamidronate, Zoledronate

Non-Aminobisphosphonates
- Etidronate, Clodronate

Question 8

Bisphosphonates
- MOA

Answer 8

Inhibits osteoclast activity
- Aminobisphosphonates:
1. Disrupts the mevalonate pathway
2. Disrupts posttranslational modification of proteins
3. interrupting cellular signaling
4. interrupts osteoclast function
5. Leads to apoptosis of osteoclasts

• Non-Aminobisphosphonates
  1. Accumulates cytotoxic metabolites within osteoclasts
  2. Interferes with osteoclast function
  3. Can lead to osteoclast cell death

Question 9

Bisphosphonates
- Indication

Answer 9

• Osteoporosis
• Paget’s Disease
• Hypercalcemia
• Primary Hyperparathyroidism (Causes bone deminierlization)

Question 10

Bisphosphonates
- Adverse Effects

Answer 10

• Gastrointestinal Issues
• Esophagitis Erosion
• Osteonecrosis of Jaw at high doses
• Aminobisphosphonates can cause a fever in first doses of IV administration

Question 11

Estrogen (Bone Disorder)
- Examples

Answer 11

Raloxifene

Question 12

Estrogen (Bone Disorder)
- MOA

Answer 12

Selective estrogen receptor modulators
- Stimulates osteoblasts
- Inhibits osteoclasts

Question 13

Estrogen (Bone Disorder)
- Adverse Effects

Answer 13

• Hot flushes, flu-like symptoms
• Thrombophlebitis / Thromboembolism

Not recommended as a primary prevention of osteoporotic fracture
- Given to postmenopausal women who can not tolerate bisphosphonate

Question 14

Parathyroid Hormone
- Examples

Answer 14

Teriparatide

Question 15

Parathyroid Hormone
- MOA

Answer 15

• Increases Serum Calcium
• Decreases Serum Phosphate
• Increases RankL causing increased Osteoclast activity

Low Dose:
- Bone Formation
High Dose (Net effect):
- Bone Resorption

Question 16

Parathyroid Hormone
- Acts on?

Answer 16

PTH acts on PTH-1 Receptors

PTH acts on osteoblasts
- Increases number of osteoblasts
- Inhibits apoptosis of osteoblasts
–> Bone Formation

PTH acts on Insulin-like growth factor (IGF-1) in osteoblasts
- Anabolic effect on bone
–>Bone Formation

PTH acts on the kidney:
- Increased Ca2+ and Mg2+ reabsorption
- Decreased phosphate, amino acids, bicarbonate, Na+, Cl-, Sulfate
- Stimulates 1,25 dihydroxyvitamin D
–> Creates more Vit D (Important for Bone Resorption)

Question 17

Parathyroid Hormone
- Indication

Answer 17

Severe osteoporosis
- Or when bisphosphonates and SERM do not work

Question 18

Parathyroid Hormone
- Contraindications

Answer 18

Children or young adults with open epiphysis

Hypercalcemia

Pregnancy

Paget’s Disease

History of radiation; risk of osteosarcoma

Question 19

Parathyroid Hormone
- Adverse Effects

Answer 19

Mild Hypercalcemia

Leg Cramps

Nausea

Orthostatic Hypotension

Question 20

Vitamin D
- MOA

Answer 20

Increases Calcium absorption from intestine, distal renal tubules,

Stimulates osteoblast (Form bone) and osteoclast (Dissolve bone)

Negative feedback: Results in decrease transcription of PTH

Result:
- Increases absorption of calcium allowing for stronger bones
- Increases muscle strength meaning less chances of falls and fractures

Question 21

Vitamin D
- Indications

Answer 21

Osteoporosis

Hyperparathyroidism

Osteomalacia (Poor mineralization of bone)

RIckets (Lack of Vitamin D)

Question 22

Vitamin D
- Side Effects

Answer 22

Hypercalcemia
- GI Pain
- Renal Stones
- Psychiatric Disturbances

Question 23

RANKL Inhibitors
- Examples

Answer 23

Denosumab

Question 24

RANKL Inhibitors
- MOA

Answer 24

1. Inhibits RANKL on osteoblasts
2. Prevents RANK (On Osteoclast) from binding RANKL (On Osteoblast)
3. Prevents differentiation, activation, and survival of osteoclasts
4. Inhibits osteoclast activity

Result: Decreased Bone Resorption

Question 25

RANKL Inhibitors
- Indication

Answer 25

Osteoporosis

Question 26

RANKL Inhibitors
- Side Effects

Answer 26

Eczema (Small risk)

Hypocalcemia

Increased Risk of Infection

Osteonecrosis of Jaw

Atypical Fractures

Question 27

Calcitonin
- Examples

Answer 27

Salcatonin

Question 28

Calcitonin
- MOA

Answer 28

Decreases reabsorption of calcium and phosphate in the kidney

Inhibits osteoclast activity
- Inhibits bone resorption

SC/IM

Question 29

Calcitonin
- Indication

Answer 29

Hypercalcemia

Paget’s Disease (Less convenient to use, just use BP)

Postmenopausal and Corticosteroid related osteoporosis (Combined with other agents)

Question 30

Calcium Salts
- Examples

Answer 30

Calcium Carbonate, Calcium Citrate, etc.

Question 31

Calcium Salts
- MOA

Answer 31

Calcium and Vitamin D:
- Essential nutrients needed for bone health

Vitamin D increases absorption on Calcium
- Results in stronger bones
- Results in stronger muscles leading to less fall and fractures

Calcium Carbonate has the highest calcium

Question 32

Calcium Salts
- Adverse Effects

Answer 32

Gastrointestinal Disturbances

Patients receiving Cardiac Glycosides (Extracellular Calcium Concentration can influence its toxicity)